Overexpressed cyclophilin B suppresses apoptosis associated with ROS and Ca2+ homeostasis after ER stress.
Prolonged accumulation of misfolded proteins in the endoplasmic reticulum (ER) results in ER stress-mediated apoptosis. Cyclophilins are protein chaperones that accelerate the rate of protein folding through their peptidyl-prolyl cis-trans isomerase (PPIase) activity. In this study, we demonstrated that ER stress activates the expression of the ER-localized cyclophilin B (CypB) gene through a novel ER stress response element. Overexpression of wild-type CypB attenuated ER stress-induced cell death, whereas overexpression of an isomerase activity-defective mutant, CypB/R62A, not only increased Ca(2+) leakage from the ER and ROS generation, but also decreased mitochondrial membrane potential, resulting in cell death following exposure to ER stress-inducing agents. siRNA-mediated inhibition of CypB expression rendered cells more vulnerable to ER stress. Finally, CypB interacted with the ER stress-related chaperones, Bip and Grp94. Taken together, we concluded that CypB performs a crucial function in protecting cells against ER stress via its PPIase activity.
Kim
Jinhwan
J
Department of Biochemistry and Molecular Biology, Medical Science and Engineering Research Center for Bioreaction to Reactive Oxygen Species, BK-21, School of Medicine, Kyung Hee University, Seoul 130-701, Korea.
Choi
Tae Gyu
TG
Ding
Yan
Y
Kim
Yeonghwan
Y
Ha
Kwon Soo
KS
Lee
Kyung Ho
KH
Kang
Insug
I
Ha
Joohun
J
Kaufman
Randal J
RJ
Lee
Jinhwa
J
Choe
Wonchae
W
Kim
Sung Soo
SS
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D021983:Cyclophilins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005786:Gene Expression Regulation; D006706:Homeostasis; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D051381:Rats; D017382:Reactive Oxygen Species; D014158:Transcription, Genetic
D017382:Reactive Oxygen Species; C081786:cyclophilin B; D021983:Cyclophilins; D002118:Calcium